Cesium carbonate → 3-Chloro-2-[7-fluoro-4-(6-methylpyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrile

HRID 626756ノート

反応式

HRID 626756 の反応式
Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])[N:10]=[C:6]2[C:5]([F:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24][N:23]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:19][C:18]1[C:11]([N:9]2[CH:8]=[C:7]3[C:2]([NH:21][C:22]4[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24][N:23]=4)=[N:3][CH:4]=[C:5]([F:20])[C:6]3=[N:10]2)=[C:12]([CH:15]=[CH:16][CH:17]=1)[C:13]#[N:14]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 5728526-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866970642-(4-Bromo-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-3-chlorobenzonitrile

生成物 1

HCID 696718283-Chloro-2-[7-fluoro-4-(6-methylpyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrile収率 47.4%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

A mixture of 2-(4-bromo-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-3-chlorobenzonitrile (158 mg, 0.45 mmol), 4-amino-6-methylpyrimidine (55 mg, 0.5 mmol), Pd2(dba)3 (10 mg, 0.011 mmol), Xantphos (26 mg, 0.045 mmol) and cesium carbonate (293 mg, 0.9 mmol) in dioxane (3 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 150° C. in the microwave for 30 minutes. The resultant mixture was partitioned between ethyl acetate and water. The layers were separated and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (80-90% ethyl acetate in cyclohexane) to afford the title compound as a beige solid (81 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.83 (s, 1H), 9.48 (d, J=2.6 Hz, 1H), 8.71 (d, J=1.2 Hz, 1H), 8.38 (s, 1H), 8.23-8.20 (m, 2H), 8.03 (d, J=3.5 Hz, 1H), 7.92 (t, J=8.1 Hz, 1H), 2.46 (s, 3H). LCMS (Method B): RT=3.04 min, m/z: 380 [M+H+].

後処理

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. customThe resultant mixture was partitioned between ethyl acetate and water
  4. customThe layers were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (80-90% ethyl acetate in cyclohexane)

出典と根拠

ORDレコード
ord-9bea88cf43204d928c9aae2734ed8de4
出典データセット
uspto-grants-2016_04
特許番号
US09309240B2

反応ノート

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